Modulatory effects of NDP-MSH in the regenerating liver after partial hepatectomy in rats

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• 作者：Caterina Lonati ; Andrea Carlin ; Patrizia Leonardi ; Franco Valenza ; Silvano Bosari ; Anna Catania ; Stefano Gatti
• 关键词：伪-MSH ; 伪-melanocyte stimulating hormone ; Atf3 ; activating transcription factor 3 ; Ccr2 ; chemokine (C&ndash ; C motif) receptor 2 ; Ctf1 ; cardiotrophin 1 ; Cxcl1 ; chemokine (C&ndash ; X&ndash ; C motif) ligand 1 ; Egr1 ; early growth response 1 ; GAPDH ; glyceraldehyde-3-phosphate dehydrogenase ; Hsp70-1 ; heat shock protein 70-1 ; IFN-纬 ; interferon gamma ; I魏B伪 ; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha ; LBWR ; liver-to-body weight ratio ; Lif ; leukemia inhibitory fac
• 刊名：Peptides
• 出版年：December, 2013
• 年：2013
• 卷：50
• 期：Complete
• 页码：145-152
• 全文大小：1399 K

文摘

Melanocortins are endogenous peptides that exert protective actions on the host physiology. The broad modulatory effects of these molecules suggest that they might influence the mediator network induced during liver regeneration. The research aim was to determine if melanocortin treatment alters liver molecular changes induced by partial hepatectomy (PH). Rats under isoflurane anesthesia were subjected to standard 70% PH or sham surgery. Animals received a single i.v. injection of Nle4,DPhe7-伪-melanocyte stimulating hormone (NDP-MSH) or saline 30 min before surgery. Sacrifice was performed at time intervals between 4 and 72 h. A preliminary screening based on TaqMan low-density array (TLDA) identified 71 transcripts altered by PH. Real-time PCR analysis revealed that NDP-MSH modulated the expression of a substantial proportion of these transcripts including several chemokines and their receptors. The critical signaling pathway interleukin-6 (IL-6)/signal transducer and activator of transcription (STAT)/suppressor of cytokine signaling (SOCS) was significantly enhanced by NDP-MSH. Further, peptide treatment considerably reduced the decline of I魏B伪 protein caused by PH. Although the final organ regeneration was not substantially affected, NDP-MSH modulated expression of cell cycle mediators and exerted subtle influences on hepatocyte replication. Most of the changes brought about by NDP-MSH, a peptide approved for clinical use, should be salutary during liver regeneration.